IFN- is a cytokine expressed in epithelial tissues and plays a central role in antiviral mucosal immune response. The expression of IFN- in the airway is impaired in chronic airway diseases (e.g., asthma, chronic obstructive pulmonary disease), which renders patients susceptible to viral infection. IL-17A is associated with asthma and chronic obstructive pulmonary disease pathogenesis; however, IL-17A regulation of IFN- expression remains unclear. The aim of the current study is to clarify IL-17A–mediated regulatory mechanisms of IFN- expression in human airway epithelial cells. In this study, we have shown that polyinosinic:polycytidylic acid (polyI:C) and influenza A virus (IAV) infection increased IFN- expression at mRNA and protein levels in primary cultures of normal human bronchial epithelial cells, whereas IL-17A attenuated polyI:C- or IAV-induced IFN- expression. IFN- receptor 1 knockdown and a JAK inhibitor, ruxolitinib, attenuated polyI:C-induced IFN- expression, confirming that a positive autocrine feedback loop, the IFN- receptor–JAK–STAT pathway, was involved in IFN- expression. In Western blotting analysis, we demonstrated that polyI:C and IAV infection induced STAT1 phosphorylation in normal human bronchial epithelial cells, whereas IL-17A suppressed polyI:C- or IAV-mediated STAT1 phosphorylation. Furthermore, we found that cotreatment with IL-17A and polyI:C or IAV infection synergistically increased suppressor of cytokine signaling (SOCS)1 and SOCS3 expression. SOCS1 small interfering RNA and SOCS3 small interfering RNA negated the inhibitory effect of IL-17A in polyI:C-induced IFN- expression by restoring attenuated STAT1 phosphorylation. Taken together, these findings indicate that IL-17A attenuates virus-induced IFN- expression by enhancing SOCS1 and SOCS3 expression to inhibit autocrine signaling loops in human airway epithelial cells.
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